Inducible protein in rat hepatomas with expression alternative to alpha-fetoprotein.
The rat hepatoma cell line McA RH7777 was cloned into alpha-fetoprotein-producing (AFP+) and non-producing (AFP-) sublines. A monoclonal antibody (MAb A2/3) reacting with an antigen (Ag A2/3) present only in AFP- clones or AFP- cells in mixed clones was obtained. Ag A2/3 was absent from the liver of embryonic, fetal, newborn and adult rats, but it was present in gastric and intestinal mucosa of adult rats. Ag A2/3 was found to be a heavy metal-inducible protein: Cd2+ and Pb2+ strongly induced the expression of Ag A2/3 in vivo in the liver of adult rats, while xenobiotics and CCl4 were not active in this respect. In vitro Cd2+ and Pb2+ induced Ag A2/3 expression in several AFP+ clones, leading to a simultaneous marked decrease of AFP+ cells from such clones. The effect of Cd2+ in the induction of Ag A2/3 and suppression of AFP was reversible. SDS PAGE revealed one protein band with an m.w. close to 45,000, which was not sensitive to mercaptoethanol. Despite its inducible properties, Ag A2/3 was shown not to belong to metallothioneins, cytochrome P-450, glutathion-transferase or heat shock proteins families, well-known as being inducible cell stress proteins. Expression of Ag A2/3 could be one of the factors determining the high amplitude of AFP production by individual liver tumors. The nature of Ag A2/3 and its alternative expression with respect to AFP remain to be studied.
Eraiser
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TL
Laboratory of Immunochemistry, Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow.
Yazova
A K
AK
Poltoranina
V S
VS
Kuprina
N I
NI
Karamova
E R
ER
Shipova
L Y
LY
Lazarevich
N L
NL
Abelev
G I
GI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D015152:Blotting, Northern; D019256:Cadmium Chloride / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D002999:Clone Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000276:immunology; D006825:Hybridomas; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D014407:Tumor Cells, Cultured; D017967:Zinc Compounds / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000096:biosynthesis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D002273:Carcinogens; D002712:Chlorides; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D017967:Zinc Compounds; D000509:alpha-Fetoproteins; C016837:zinc chloride; D019256:Cadmium Chloride